The present invention relates to metal-containing ribonucleotide polypeptides (RNP) and processes for their preparation, their use and medicaments containing ribonucleotide polypeptides or their molecular-biological equivalent structures and/or parts and/or derivatives.
Tissue homeostasis of the body, its organs and tissue depends on the regulation mechanisms of angiogenesis. This influences both tissue repair and wound healing, formation of new tissue in embryogenesis and the reproductive cycles and growth, retrogression and destruction of tumours, transplants and vascularised and non-vascularised tissues.
Hitherto, no non-mitogenic mediators have yet been found, with which influence of tissue homeostasis is possible, that is induction and regulation of vascular growth.
The object of the present invention is therefore to provide a non-mitogenic mediator of tissue homeostasis, with which primarily tissue repair, wound healing, angiogenesis and neovascularisation may be influenced. A further object of the invention is the provision of a process for producing the non-mitogenic mediators and a medicament containing this non-mitogenic mediator.
These aims are achieved by the objects of the patent claims.
It has been found by the inventors that there are non-mitogenic cellular mediators based on nucleic acid of defined sequence, which may cause specifically the formation of blood vessels in vivo and in vitro and represent biologically specific, naturally acting non-mitogenic mediators of angiogenesis or the directional growth of blood vessel branches.
The new class of cellular morphogens for endothelial cells proven by the inventors exists in the form of a bioactive metal ribonucleotide peptide (RNP). This is called angiotropin.
The structure of angiotropin may be assigned to the ribonucleotide proteins (RNP). It consist of a protein part (ARP=Angiotropin Related Protein) and an RNA part (ARNA=Angiotropin RNA). Cu(II) is essential for formation of the complex of ARP and ARNA. In addition to the copper ion, angiotropin contains a Ca(II) ion. Mg(II) ions are also useful for the diverse biological and biochemical functions of angiotropin.
The protein part (ARP) consists of a protein which may be assigned to the family of S100 proteins (Dell""Angelica et al., Journal of Biological Chemistry, Volume 269, No. 46, page 28929-28936 (1994)) and is preferably 91 amino acids long. The primary structure of this preferred ARP is as follows: